Publications by authors named "Jun Teruya"

82 Publications

Trimester-specific thromboelastic values and coagulation activation markers in pregnancy compared across trimesters and compared to the nonpregnant state.

Int J Lab Hematol 2021 Jan 25. Epub 2021 Jan 25.

The Department of Medicine, Texas Children's Hospital and Baylor College of Medicine, Houston, TX, USA.

Introduction: Rotational thromboelastometry (ROTEM) rapidly identifies deficits underlying coagulopathy during massive hemorrhage. Prompt coagulopathy correction is balanced with the risk of blood product overutilization, making the ability to quickly target therapy highly desirable. However, data about ROTEM reference ranges in pregnancy are limited. We hypothesized that ROTEM parameters change across trimesters of pregnancy and differ from the nonpregnant state. Also, we sought to identify which hemostatic test best predicts coagulation activation during pregnancy.

Methods: A prospective cohort study in healthy pregnant patients in the first (n = 34), second (n = 34), and third trimesters (n = 41) against healthy, nonpregnant controls (n = 33) was performed. Citrated blood was collected, and ROTEM, complete blood count, and plasma-based assays of coagulation were performed. Mean ± SD or median [IQR] were compared across trimesters and between each trimester against the nonpregnant state. ROTEM parameters vs. plasma-based assays were also compared.

Results: Maximum clot firmness and A10 in FIBTEM correlated strongly with fibrinogen level. INTEM and EXTEM values demonstrated only weak to modest correlation with corresponding tests using plasma assays. Thrombin antithrombin complex (TAT) increased from the first trimester onward, whereas other coagulation activation markers did not show difference compared with control group.

Conclusion: Rotational thromboelastometry parameters differ variably across trimesters of pregnancy and compared with the nonpregnant state. The development and use of pregnancy-specific values are critical to the proper clinical interpretation of ROTEM in women with serious hemorrhage during different stages in pregnancy. TAT was the earliest laboratory marker for coagulation activation among others.
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http://dx.doi.org/10.1111/ijlh.13472DOI Listing
January 2021

Evaluation and Management of Coagulopathies and Thrombophilias in Pediatric Patients.

Clin Lab Med 2021 Mar 15;41(1):83-100. Epub 2020 Dec 15.

Pathology & Immunology, Baylor College of Medicine, 6621 Fannin Street, Houston, TX 77030, USA. Electronic address:

The diagnosis of coagulopathy or thrombophilia in pediatric patients can be challenging. Congenital coagulopathies often present in the pediatric period and require appropriate work-up for diagnosis and ongoing management. Acquired coagulopathies of childhood are frequently encountered in hospitalized children and warrant appropriate coagulation testing for goal-directed therapy. The incidence of thrombosis is increasing in pediatric patients. After identifying the presence of thrombus, acute management includes initiating therapeutic anticoagulation. Choice of anticoagulant depends on patient's clinical status, along with availability of the anticoagulant. Thrombophilia evaluation is performed when children present with spontaneous thrombosis. Thrombophilia tests are inaccurate during acute illness.
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http://dx.doi.org/10.1016/j.cll.2020.10.006DOI Listing
March 2021

Low antithrombin levels in neonates and infants undergoing congenital heart surgery result in more red blood cell and plasma transfusion on cardiopulmonary bypass.

Transfusion 2020 Dec 17;60(12):2841-2848. Epub 2020 Sep 17.

Department of Pathology, Texas Children's Hospital, Houston, Texas, USA.

Background: Neonates have lower levels of antithrombin (AT) due to immature liver synthetic function. AT deficiency may lead to inadequate anticoagulation with heparin during cardiac surgery resulting in consumption of coagulation factors and increased blood transfusion. The goal of this study is to examine the effect of AT level on the transfusion requirements of neonates and infants undergoing open heart surgery.

Study Design And Methods: This is a prospective, observational study at a tertiary pediatric referral center. Neonates and infants up to 6 months of age undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were enrolled. Demographic, intraoperative, transfusion, and complications data were collected. Preoperative AT level was measured after induction of anesthesia. Prior to separation from CPB, a second blood sample was drawn and AT, thrombin antithrombin complex (TAT), D-dimer, and anti-Xa levels were measured. Linear and logistic regression were performed for data analysis.

Results: Preoperative low AT level was significantly associated with increased transfusion of red blood cells (RBCs) and fresh frozen plasma (FFP) during CPB, but not after separation from CPB. The incidence of thrombosis and re-operation were not associated with preoperative AT levels. There was no association between TAT, D-dimer, and anti-Xa levels at the end of CPB and preoperative AT levels.

Conclusion: Low preoperative AT level is associated with increased transfusion of RBC and FFP on CPB in neonates and infants undergoing congenital heart surgery. Low preoperative AT level did not result in coagulation activation after CPB and after surgery.
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http://dx.doi.org/10.1111/trf.16082DOI Listing
December 2020

C-reactive protein-induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by elevated factor VIII.

Int J Lab Hematol 2021 Feb 19;43(1):139-142. Epub 2020 Aug 19.

Departments of Pathology & Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.

Introduction: Activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) activity are used to monitor unfractionated heparin therapy in children on extracorporeal membrane oxygenation (ECMO). Elevated C-reactive protein (CRP) can prolong aPTT and cause discrepancy between these two assays. We aimed to evaluate CRP effect on aPTT and anti-Xa assays in the presence of heparin and to determine whether elevated CRP affects laboratory monitoring in pediatric ECMO patients.

Materials And Methods: Citrated normal specimens were spiked with CRP, heparin, and recombinant factor VIII (FVIII) and followed by measurement of aPTT and anti-Xa activity. Additionally, aPTT, anti-Xa activity, FVIII, fibrinogen, and CRP were measured in 18 ECMO specimens.

Results: Elevated CRP prolonged aPTT in normal specimens with or without heparin, but did not affect anti-Xa assay. In contrast, ECMO specimens showed similar aPTT and anti-Xa values regardless of CRP level. Elevated CRP in specimens was accompanied by increased fibrinogen and FVIII activity. Additional in vitro experiments confirmed that FVIII spiked simultaneously with CRP attenuated CRP-induced aPTT prolongation in heparinized specimens.

Conclusion: In vitro CRP-induced aPTT prolongation is not observed in pediatric ECMO samples due to concomitant FVIII increase. Discordant changes of CRP and FVIII in plasma could contribute to aPTT/anti-Xa discrepancies observed during heparin therapy in the pediatric population. The anti-Xa assay is preferable for heparin monitoring in pediatric ECMO settings.
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http://dx.doi.org/10.1111/ijlh.13314DOI Listing
February 2021

Structural characterization of a clinically described heparin-like substance in plasma causing bleeding.

Carbohydr Polym 2020 Sep 19;244:116443. Epub 2020 May 19.

Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Biology, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA. Electronic address:

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it had an intermediate between heparin and HS with low antithrombin-mediated anticoagulant activity. We speculate that this 10-year old patient might have a platelet function defect influenced by this unusual HS. Endothelial defects not measurable by our methods might have also contributed to the observed bleeding complications.
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http://dx.doi.org/10.1016/j.carbpol.2020.116443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337982PMC
September 2020

Blood, Sweat, and Fears: A Novel Mutation Associated With Anaphylaxis and Nonresponse in a Patient With Afibrinogenemia.

J Pediatr Hematol Oncol 2021 Mar;43(2):e260-e263

Baylor College of Medicine.

Congenital afibrinogenemia is a rare disorder characterized by a lack of detectable fibrinogen. The mainstay of treatment for acute bleeding episodes or perioperative management is replacement with fibrinogen concentrate or fibrinogen-containing blood products. The development of neutralizing antibodies and severe allergic reactions to fibrinogen replacement is rarely reported in afibrinogenemia patients. Here the treatment regimen is described for a 6-year-old girl with a severe allergic reaction to multiple fibrinogen-containing products who became refractory to treatment because of a presumed inhibitor to fibrinogen.
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http://dx.doi.org/10.1097/MPH.0000000000001812DOI Listing
March 2021

Tortuosity-powered microfluidic device for assessment of thrombosis and antithrombotic therapy in whole blood.

Sci Rep 2020 04 1;10(1):5742. Epub 2020 Apr 1.

Department of Biomedical Engineering, Texas A&M College of Engineering, College Station, TX, USA.

Accurate assessment of blood thrombosis and antithrombotic therapy is essential for the management of patients in a variety of clinical conditions, including surgery and on extracorporeal life support. However, current monitoring devices do not measure the effects of hemodynamic forces that contribute significantly to coagulation, platelet function and fibrin formation. This limits the extent to which current assays can predict clotting status in patients. Here, we demonstrate that a biomimetic microfluidic device consisting stenosed and tortuous arteriolar vessels would analyze blood clotting under flow, while requiring a small blood volume. When the device is connected to an inline pressure sensor a clotting time analysis is applied, allowing for the accurate measurement of coagulation, platelets and fibrin content. Furthermore, this device detects a prolonged clotting time in clinical blood samples drawn from pediatric patients on extracorporeal membrane oxygenation receiving anticoagulant therapy. Thus, this tortuosity activated microfluidic device could lead to a more quantitative and rapid assessment of clotting disorders and their treatment.
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http://dx.doi.org/10.1038/s41598-020-62768-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113244PMC
April 2020

Monitoring bivalirudin therapy in children on extracorporeal circulatory support devices: Thromboelastometry versus routine coagulation testing.

Thromb Res 2020 02 12;186:54-57. Epub 2019 Dec 12.

Department of Pathology & Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, United States of America.

Introduction: Bivalirudin is an alternative to heparin anticoagulation in infants and children in the setting of extracorporeal life support (ECLS). While activated partial thromboplastin time (aPTT) is widely accepted as the standard test to monitor bivalirudin therapy, the usefulness of thromboelastometry (ROTEM) to monitor bivalirudin infusion in the setting of ECLS is unknown.

Objective: We aimed to assess the utility of ROTEM in monitoring hemostasis and bivalirudin effect in children on either extracorporeal membrane oxygenation (ECMO) or ventricular assist devices (VAD) compared to standard plasma based coagulation assays.

Methods: A retrospective study of children undergoing bivalirudin infusion for ECMO/VAD support from a tertiary care pediatric hospital (January 2017-June 2018) was performed. ROTEM assays for extrinsic (EXTEM) and intrinsic (INTEM) coagulation pathways, INTEM with heparinase (HEPTEM), fibrin formation (FIBTEM) with measurement of the clotting time (CT) and maximum clot firmness (MCF) were compared to routine hemostasis testing including: aPTT, aPTT Hepzyme (HPTT), prothrombin time (PT), fibrinogen and platelet count.

Results: One hundred and six blood samples from 18 children were tested. There was a strong positive correlation between HPTT and HEPTEM CT, and moderate correlation between aPTT and INTEM CT. The bivalirudin dose did not correlate with any test, but displayed strong age-dependence, with infants requiring higher doses of bivalirudin to maintain therapeutic targets. Excellent correlation was found between FIBTEM MCF values and fibrinogen, but FIBTEM overestimated fibrinogen level when platelet count was >300 × 10/L. Heparin-like effect was identified in 39% of specimens, and an improved correlation between aPTT and INTEM CT was observed in specimens without heparinoids.

Conclusions: In the setting of bivalirudin therapy, prolongation of CT on INTEM and HEPTEM showed moderate to strong correlation with aPTT and HPTT, and therefore, may provide a good alternative to these assays. In addition, HPTT and HEPTEM CT might be preferable for monitoring bivalirudin in the setting of ECLS due to frequent detection of heparin-like effect.
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http://dx.doi.org/10.1016/j.thromres.2019.12.007DOI Listing
February 2020

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation.

Semin Thromb Hemost 2020 Feb 13;46(1):62-72. Epub 2019 Dec 13.

Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.

Cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) cause hemostatic derangements that can predispose patients to both bleeding and thrombotic complications. Often, patients present for urgent surgery while taking medications including antiplatelet agents, vitamin K antagonists, and direct oral anticoagulants, which must be recognized, monitored, and managed. During extracorporeal circulation, appropriate anticoagulation, most commonly with heparin, is required to maintain blood flow and avoid thrombotic complications. However, anticoagulation and other effects of extracorporeal circuits can also have an undesired consequence of bleeding. Extracorporeal circulation leads to coagulopathy that may require therapy with blood products such as platelets, cryoprecipitate, and plasma in case a patient bleeds. Platelet dysfunction related to exposure to a foreign circuit is a primary concern, as is the development of acquired von Willebrand syndrome, which frequently remains undetected on routine testing. Hemorrhagic complications in ECMO, such as intracranial hemorrhage, pulmonary hemorrhage, and hemithorax, can occur. Hemostatic agents including antifibrinolytics, desmopressin, fibrinogen concentrates, and other factor concentrates may be needed to achieve hemostasis in these often-challenging patients. Managing bleeding on extracorporeal support requires careful monitoring and a thoughtful approach.
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http://dx.doi.org/10.1055/s-0039-3400273DOI Listing
February 2020

Editorial: Hemostasis in ECMO and VAD.

Front Med (Lausanne) 2019 25;6:143. Epub 2019 Jun 25.

Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.3389/fmed.2019.00143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604765PMC
June 2019

Acquired von Willebrand Syndrome in Pediatric Extracorporeal Membrane Oxygenation Patients: A Single Institution's Experience.

Pediatr Crit Care Med 2019 10;20(10):980-985

Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Objectives: 1) Describe the prevalence of acquired von Willebrand syndrome in pediatric patients undergoing extracorporeal membrane oxygenation deemed to be at increased risk for the disease in our institution, 2) discuss the challenges of testing for acquired von Willebrand syndrome diagnosis, 3) describe the characteristics of the patient population found to have acquired von Willebrand syndrome and their outcomes, and 4) discuss the potential implications of acquired von Willebrand syndrome on bleeding complications.

Design: Retrospective chart review.

Setting: PICU and cardiovascular ICU in a single institution.

Patients: All PICU and cardiovascular ICU extracorporeal membrane oxygenation patients 0-18 years old who underwent screening for acquired von Willebrand syndrome between January 2014 and December 2016.

Interventions: Humate P administration to a small subset of acquired von Willebrand syndrome positive subjects.

Measurements And Main Results: Laboratory data of identified patients were analyzed. The diagnosis of acquired von Willebrand syndrome was made based on decreased ristocetin cofactor activity to von Willebrand factor antigen ratio and/or abnormal multimer analysis. Clinical data were extracted from the chart and through the Pediatric Extracorporeal Membrane Oxygenation Outcome Registry to describe the demographics, comorbidities, and outcomes of this patient population. In the 2 years, 29 patients had laboratory testing performed for surveillance and in cases of clinical bleeding. Of these, 23 (79%) were positive by criteria. No significant difference in mortality rate was found between patients with acquired von Willebrand syndrome versus without. We also did not find a significant difference in the blood product utilization or bleeding complications between patients with acquired von Willebrand syndrome versus without. Humate P was administered in 39% of patients (9/23) who were positive for acquired von Willebrand syndrome, but no significant difference was seen in blood product utilization or bleeding complications between acquired von Willebrand syndrome patients receiving Humate P versus those who did not.

Conclusions: Acquired von Willebrand syndrome is a common but under recognized disorder in pediatric extracorporeal membrane oxygenation patients. The clinical implications of this disorder on bleeding and its potential treatments are still unclear.
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http://dx.doi.org/10.1097/PCC.0000000000002009DOI Listing
October 2019

Antithrombin Population Pharmacokinetics in Pediatric Ventricular Assist Device Patients.

Pediatr Crit Care Med 2019 12;20(12):1157-1163

Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Objectives: Describe the pharmacokinetics of antithrombin in pediatric patients undergoing ventricular assist device therapy and provide dosing recommendations for antithrombin in this population.

Design: A retrospective population pharmacokinetic study was designed.

Setting: Large tertiary care children's hospital Subject inclusion criteria consisted of less than 19 years old.

Patients: Subjects less than 19 years old undergoing therapy with a HeartWare ventricular assist device (HeartWare, Framingham, MA) or Berlin EXCOR ventricular assist device (Berlin GmbH, Berlin, Germany), who received a dose of antithrombin with a postdose antithrombin activity level from January 1, 2011, to June 30, 2017.

Interventions: Population pharmacokinetic analysis and simulation using NONMEM v.7.4 (Icon, PLC, Dublin, Ireland).

Measurements And Main Results: A total of 41 patients met study criteria (median age, 5.8 years [interquartile range, 1.6-9.9 yr]), and 53.7% underwent therapy with the pulsatile Berlin EXCOR pediatric ventricular assist device (Berlin Heart GmbH, Berlin, Germany). All patients received unfractionated heparin continuous infusion at a mean ± SD dose of 29 ± 14 U/kg/hr. A total of 181 antithrombin doses (44.1 ± 24.6 U/kg/dose) were included, and baseline antithrombin activity levels were 77 ± 12 U/dL. Antithrombin activity levels were drawn a median 19.9 hours (interquartile range, 8.8-41.6 hr) after antithrombin dose. A one-compartment proportional error model best fit the data, with allometric scaling of fat-free mass providing a better model fit than actual body weight. Unfractionated heparin and baseline antithrombin were identified as significant covariates. A 50 U/kg dose of antithrombin had a simulated half-life 13.2 ± 6.6 hours.

Conclusions: Antithrombin should be dosed on fat-free mass in pediatric ventricular assist device patients. Unfractionated heparin dose and baseline antithrombin activity level should be considered when dosing antithrombin in pediatric ventricular assist device patients.
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http://dx.doi.org/10.1097/PCC.0000000000002039DOI Listing
December 2019

Maternal outcomes in unexpected placenta accreta spectrum disorders: single-center experience with a multidisciplinary team.

Am J Obstet Gynecol 2019 10 4;221(4):337.e1-337.e5. Epub 2019 Jun 4.

Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX. Electronic address:

Objective: In a 2015 Maternal-Fetal Medicine Units Network study, only half of placenta accreta spectrum cases were suspected before delivery, and the outcomes in the anticipated cases were paradoxically poorer than in unanticipated placenta accreta spectrum cases. This was possibly because the antenatally suspected cases were of greater severity. We sought to compare the outcomes of expected vs unexpected placenta accreta spectrum in a single large US center with multidisciplinary management protocol.

Study Design: This was a retrospective cohort study carried out between Jan. 1, 2011, and June 30, 2018, of all histology-proven placenta accreta spectrum deliveries in an academic referral center. Patients diagnosed at the time of delivery were cases (unexpected placenta accreta spectrum), and those who were antentally diagnosed were controls (expected placenta accreta spectrume). The primary and secondary outcomes were the estimated blood loss and the number of red blood cell units transfused, respectively. Variables are reported as median and interquartile range or number (percentage). Analyses were made using appropriate parametric and nonparametric tests.

Results: Fifty-four of the 243 patients (22.2%) were in the unexpected placenta accreta spectrum group. Patients in the expected placenta accreta spectrum group had a higher rate of previous cesarean delivery (170 of 189 [89.9%] vs 35 of 54 [64.8%]; P < .001) and placenta previa (135 [74.6%] vs 19 [37.3%]; P < .001). There was a higher proportion of increta/percreta in expected placenta accreta spectrum vs unexpected placenta accreta spectrum (125 [66.1%] vs 9 [16.7%], P < .001). Both primary outcomes were higher in the unexpected placenta accreta spectrum group (estimated blood loss, 2.4 L [1.4-3] vs 1.7 L [1.2-3], P = .04; red blood cell units, 4 [1-6] vs 2 [0-5], P = .03).

Conclusion: Our data contradict the Maternal-Fetal Medicine Units results and instead show better outcomes in the expected placenta accreta spectrum group, despite a high proportion of women with more severe placental invasion. We attribute this to our multidisciplinary approach and ongoing process improvement in the management of expected cases. The presence of an experienced team appears to be a more important determinant of maternal morbidity in placenta accreta spectrum than the depth of placental invasion.
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http://dx.doi.org/10.1016/j.ajog.2019.05.035DOI Listing
October 2019

Severe hypocalcemia during surgery for placenta accreta spectrum: The case for empiric replacement.

Acta Obstet Gynecol Scand 2019 10 23;98(10):1326-1331. Epub 2019 May 23.

Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.

Introduction: We aimed to determine predictive factors for severe hypocalcemia in women with placenta accreta spectrum.

Material And Methods: Study of 123 women with histology-proven placenta accreta spectrum with cesarean hysterectomy between 2011 and 2017. Two groups were selected: Cases: critically low ("panic value") serum total calcium (≤7 mg/dL) and Controls: normal serum total calcium (≥8.5 mg/dL). Regression and receiver operating characteristic (ROC) analyses were performed to evaluate the potential associations.

Results: There were 13 women with critically low (cases) and 18 with normal calcium (controls). Baseline characteristics were not statistically different. The median estimated blood loss, units of red blood cells (RBCs) transfused and volume of crystalloid transfused, were higher in the low calcium group. Six out of 13 (46.2%) cases had received ≥4 units of RBCs during surgery vs 2 of 18 (11.1%) controls (P = 0.04). ROC analysis showed that estimated blood loss, units of RBCs transfused, and crystalloid transfused were associated with severe hypocalcemia and univariate regression analysis confirmed that estimated blood loss ≥1500 mL, RBC transfusion ≥4 units, and crystalloid transfused ≥4L were associated with severe hypocalcemia.

Conclusions: Intraoperative transfusion of ≥4 units RBCs is predictive of the development of severe hypocalcemia in placenta accreta spectrum patients experiencing active bleeding. Empiric replacement of 1 g CaCL is recommended for every 4 U RBC transfused.
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http://dx.doi.org/10.1111/aogs.13636DOI Listing
October 2019

Coagulopathy in surgical management of placenta accreta spectrum.

Eur J Obstet Gynecol Reprod Biol 2019 Jun 19;237:126-130. Epub 2019 Apr 19.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, United States.

Background: One of the major complications of the placenta accreta spectrum (PAS) is the development of coagulopathy. The detection, prevention and prompt treatment of coagulopathy may be lifesaving.

Objective: Our objective was to study selected factors associated with coagulopathy in the management of PAS by a well-established multidisciplinary team.

Study Design: This is a retrospective review of all patients with pathologically proven PAS (including placenta accreta, increta or percreta) who underwent surgery by our multidisciplinary team between January 2011 and February 2017. Coagulopathy in this setting was defined as a platelet count of <100,000/mm, international normalized ratio >1.5, and/or fibrinogen <300 mg/dL based on institutional protocols developed by our Division of Transfusion Medicine & Coagulation. The outcomes of those patients with and without coagulopathy were compared with appropriate adjustments. Receiver operating characteristics curves (ROCs) were constructed to assess the ability of select variables to discriminate between women with and without coagulopathy, and the area under the curves (AUCs) were calculated.

Results: Of 123 singleton patients with PAS, 37 (30.1%; 95%CI 22.1-39.0) developed coagulopathy and 86 (69.9%; 95%CI 61.0-77.9) did not. Baseline patient demographic characteristics did not differ significantly between these groups. Estimated blood loss (median and Inter-quartile range) was 2100cc (1800, 400) and 1400 (1000, 2500) in the presence and absence of coagulopathy, respectively (P < 0.01). The overall number of units of red blood cells (RBC) transfused was greatest in the coagulopathy group [3 (2, 9) vs. 1 (0, 4); P < 0.01]. Univariate regression analysis confirmed the association between coagulopathy and (i) the number of units of RBC's transfused, and (ii) the estimated blood loss. ROC curves showed that an estimated blood loss ≥ 1500 mL had the best discriminating power. Depth and/or severity of placental invasion were not associated with coagulopathy in patients with PAS.

Conclusions: Coagulopathy in patients with PAS undergoing hysterectomy is strongly associated with blood loss and replacement. It may be prudent to establish protocols that aggressively monitor for, and treat, coagulopathy when EBL exceeds 1500 mL in such surgeries, prior to the development of clinical coagulopathy which if uncorrected may lead to massive blood loss.
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http://dx.doi.org/10.1016/j.ejogrb.2019.04.026DOI Listing
June 2019

Centrifugal-flow ventricular assist device support in children: A single-center experience.

J Thorac Cardiovasc Surg 2019 04 27;157(4):1609-1617.e2. Epub 2018 Dec 27.

Congenital Heart Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.

Background: Our institutional policy is to continue centrifugal-flow ventricular assist device support for 3 months or more without activation on the transplant wait-list for physical recovery and assessment of possible myocardial recovery. We evaluated our single-institutional outcomes with centrifugal-flow ventricular assist device support in children.

Methods: Prospectively collected outcomes data in consecutive patients aged 18 years or less with centrifugal-flow ventricular assist device support were reviewed.

Results: There were 40 implantations in 39 patients (28 with cardiomyopathy, 11 with congenital heart disease, including 3 with univentricular physiology). The median support was 8 months (range, 1-79), with 13 patients (33%) supported for 12 months or more and a cumulative duration of 41 patient-years. The median age and weight at implantation were 11 (4-18) years and 35 (14-98) kg, respectively. The median body surface area was 1.1 (0.7-2.2) m, with 16 patients (40%) having a body surface area less than 1.0 m. Thirty-four patients (85%) had Interagency Registry for Mechanically Assisted Circulatory Support 1 or 2. Children with congenital heart disease were significantly smaller (P < .01) and had more prior cardiac interventions (P < .01) than those with cardiomyopathy. There were 2 early mortalities (5%) in children with cardiomyopathy. Of the 38 patients with successful implantations, 36 (95%) were discharged home and managed as outpatients. Overall adverse event rates were 5.1 (bleeding), 0.8 (device malfunction), 6.1 (infection), 3.9 (neurologic dysfunction), and 1.0 (renal dysfunction) (per 100 patient-month). In the 21 patients with cardiomyopathy supported for 3 months or more, 5 (24%) experienced normalization of left ventricular function; 4 underwent successful explantation, and 1 remains on support.

Conclusions: This study demonstrates favorable outcomes of centrifugal-flow ventricular assist device support in children, including those with congenital heart disease, with an increased incidence of cardiac recovery.
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http://dx.doi.org/10.1016/j.jtcvs.2018.12.045DOI Listing
April 2019

Coagulation and Bleeding Management in Pediatric Extracorporeal Membrane Oxygenation: Clinical Scenarios and Review.

Front Med (Lausanne) 2018 11;5:361. Epub 2019 Jan 11.

Division of Transfusion Medicine & Coagulation, Texas Children's Hospital, Houston, TX, United States.

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure that requires careful coagulation management. Indications for ECMO continue to expand, leading to more complicated patients treated by ECMO teams. At our pediatric institution, we utilize a Coagulation Team to guide anticoagulation, transfusion and hemostasis management in an effort to avoid the all-to-common complications of bleeding and thrombosis. This team formulates a coagulation plan in conjunction with a multidisciplinary ECMO team after careful review of all available laboratory data as well as the patient's clinical status. Here, we present our general strategies for ECMO management in various clinical scenarios and a review of the literature pertaining to coagulation management in the pediatric ECMO setting.
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http://dx.doi.org/10.3389/fmed.2018.00361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340094PMC
January 2019

Deficiency of complement factor H-related proteins and autoantibody-positive hemolytic uremic syndrome in an infant with combined partial deficiencies and autoantibodies to complement factor H and ADAMTS13.

Clin Kidney J 2018 Dec 7;11(6):791-796. Epub 2018 Mar 7.

Baylor College of Medicine, Houston, TX, USA.

A 3-month-old male infant developed an extremely severe episode of atypical hemolytic uremic syndrome (aHUS) associated with partial deficiencies of full-length complement factor H (FH; ∼15% of infant normal) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) (39% of normal) and autoantibodies reactive with both proteins. His FH and ADAMTS13 genes were normal, indicating that the partial deficiencies were acquired, probably as the result of autoantibodies against full-length FH and ADAMTS13. The child also had a homozygous deletion of the complement factor H-related (CFHR)3-CFHR1 portion in the complement factor H () gene cluster. He therefore had deficiency of CFHR proteins and autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) with an unusual early onset associated with a partial deficiency of ADAMTS13 and an anti-ADAMTS13 autoantibody. His clinical episode of aHUS responded to plasma infusion and subsequent treatment with mycophenolate and rituximab. We believe that this is the first report of DEAP-HUS in an infant with partial deficiencies in both ADAMTS13 and full-length FH acquired in association with autoantibodies to both proteins.
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http://dx.doi.org/10.1093/ckj/sfy010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275444PMC
December 2018

Therapeutic Plasma Exchange does not Improve Renal Function in Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy: An Institutional Experience.

Biol Blood Marrow Transplant 2019 01 23;25(1):157-162. Epub 2018 Aug 23.

Department of Pediatrics, Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplant (HSCT) that causes severe multiorgan injury. The kidneys are almost universally affected. There is no proven therapy, but therapeutic plasma exchange (TPE) is commonly used to treat TA-TMA at Texas Children's Hospital (TCH). To date, there have been no studies assessing the long-term efficacy of TPE in preventing the development of chronic kidney disease (CKD) in TA-TMA patients. In this study we retrospectively analyzed the incidence of CKD in TA-TMA pediatric patients treated with TPE to determine if this treatment modality improves renal morbidity. We reviewed records between January 2007 and June 2017 of pediatric HSCT patients diagnosed with TA-TMA, identified through an internal database maintained at TCH. To be included patients must have completed a course of TPE per the "TPE in TA-TMA" institutional protocol at TCH. CKD was defined as kidney damage for at least 3 months and stratified into stages 1 through 5 according to estimated glomerular filtration rate. Stages 4 and 5 were considered "severe CKD." In the 10-year timeframe 15 patients with TA-TMA completed a course of TPE per our institutional protocol and were subsequently followed for a median of 963 days. Fourteen patients developed CKD, and 5 of these 14 patients developed severe CKD. The cumulative incidence of severe CKD development was 33% (95% confidence interval. 11% to 57%). 6 patients required dialysis, and 2 patients received a renal transplant. 5 patients received eculizumab in addition to TPE. In our patients a TPE course of at least 7 weeks (and up to 25 weeks) was not effective in the prevention of CKD. Our data indicate a need for alternative therapeutic measures to prevent the development of CKD in TA-TMA patients.
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http://dx.doi.org/10.1016/j.bbmt.2018.08.016DOI Listing
January 2019

In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study.

Artif Organs 2018 Nov 12;42(11):1028-1034. Epub 2018 Aug 12.

Division of Congenital Heart Surgery, Texas Children's Hospital, Houston, TX, USA.

Development of pediatric ventricular assist devices (VADs) has significantly lagged behind that of adult devices. This frustrating reality is reflected by the fact that the Berlin Heart EXCOR VAD is currently the only approved pediatric-specific device in the USA. An alternative option is an off-label use of adult continuous-flow VADs, such as HeartMate II (HMII), which inevitably causes patient-device size mismatch in small children. We sought to conduct in vitro hemocompatibility testing in a pediatric flow condition, with a specific aim to provide benchmark values for future pediatric device development. Given the aforementioned fact that both pulsatile and continuous-flow devices are being used in the pediatric population, we opted to test both types of devices in the present study. The EXCOR and HMII blood pumps were tested using bovine blood under constant hemodynamic conditions (flow rate, Q = 2.5 ± 0.25L/min; differential pressure across the pump, ΔP = 68 ± 5mm Hg). Hemolysis was measured by Harboe assay. There was a steady increase in plasma free hemoglobin during in vitro testing, with a statistically significant difference between 5 and 360 min for both EXCOR (P < 0.0001) and HMII (P < 0.001). However, the degree of an increase in plasma free hemoglobin was more significant with HMII (P < 0.001). Normalized index of hemolysis for EXCOR and HMII were 0.003 ± 0.0026g/100 L and 0.085 ± 0.0119g/100 L, respectively. There was also a steady increase in platelet activation detected by CAPP2A antibody using flow cytometry, with a statistically significant difference between 5 and 360 min for both devices (P < 0.05). The degree of an increase in platelet activation was similar between the two devices (P = 0.218). High molecular weight von Willebrand factor (HMW vWF) multimer degradation measured by immunoblotting was evident for both devices, however, it was more pronounced with the EXCOR. EXCOR blood samples from all three time points (120, 240, and 360 min) were significantly different from the baseline (5 min), whereas only 360 min samples had a significant difference from the baseline with the HMII. In conclusion, we have observed similarities and differences in hemocompatibility profiles between the EXCOR and HMII, both of which are commonly used in the pediatric population. We anticipate the benchmark values in the present study will facilitate future pediatric VAD development.
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http://dx.doi.org/10.1111/aor.13165DOI Listing
November 2018

ABO-incompatible deceased donor pediatric liver transplantation: Novel titer-based management protocol and outcomes.

Pediatr Transplant 2018 11 2;22(7):e13263. Epub 2018 Aug 2.

Section of Pediatric Allergy & Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.

ABO-ILT have re-emerged as an alternate option for select patients awaiting transplant. However, treatment protocols for children undergoing deceased donor ABO-ILT are not standardized. We implemented a novel IS protocol for children undergoing deceased donor ABO-ILT based on pretransplant IH titers. Children with high pretransplant IH titers (≥1:32) underwent an enhanced IS protocol including plasmapheresis, rituximab, IVIG, and mycophenolate, while children with IH titers ≤1:16 received steroids and tacrolimus. We retrospectively assessed our outcomes of ABO-ILT with ABO-compatible recipients of similar age and diagnosis over a 2-year period. Ten children with median age of 8.9 months underwent ABO-ILT, 4 of 10 patients underwent enhanced IS due to high IH titers. Rates of complications (rejection, infections, biliary, and vascular) at both 1 year and up to 3 years post-transplant were comparable between the groups. Patients with ABO-ILT had good graft function with 100% survival at a median follow-up of 3.3 years. In conclusion, IS tailored to pretransplant IH titers in pediatric deceased donor ABO-ILT is feasible and can achieve outcomes similar to ABO-CLT at 1 and 3 years post-transplantation.
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http://dx.doi.org/10.1111/petr.13263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197909PMC
November 2018

Perturbation of Hemostatic Function by Nonbiologic Surfaces.

Semin Thromb Hemost 2018 02 1;44(1):5-6. Epub 2018 Feb 1.

Division of Transfusion Medicine & Coagulation, Texas Children's Hospital, Houston, Texas.

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http://dx.doi.org/10.1055/s-0037-1608799DOI Listing
February 2018

Management of Hemostasis for Pediatric Patients on Ventricular-Assist Devices.

Semin Thromb Hemost 2018 Feb 17;44(1):30-37. Epub 2017 Nov 17.

Division of Transfusion Medicine & Coagulation, Department of Pathology & Immunology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.

Ventricular-assist devices (VADs) have seen increased utilization in the pediatric population. Formerly, this therapeutic modality was limited to only the pulsatile VAD, EXCOR (Berlin Heart GmbH). However, the continuous flow VAD devices, HeartMate II (Abbott Inc.) and HeartWare (Medtronic Inc.), are now increasingly used in this population. Postoperatively, VAD patients are acutely anticoagulated using unfractionated heparin, often beginning 24 to 48 hours after VAD placement. Once the patient is stabilized and ready to transition to a lower acuity or outpatient setting, low-molecular-weight heparin or warfarin therapy may be instituted. Also, because of the risk for thrombotic and thromboembolic complications, antiplatelet strategies are employed using medications such as aspirin, clopidogrel, or dipyridamole. Platelet-rich plasma or whole blood platelet aggregation studies, platelet function analyzer-100 (Siemens), VerifyNow (Accriva Diagnostics), or thromboelastography platelet mapping (Haemonetics) may be used to help monitor antiplatelet effects, though the interpretation of the strength of the antiplatelet effect remains difficult. Care must be taken to monitor the hematologic complications of VAD, including acquired von Willebrand syndrome, which increases the risk for bleeding, and intravascular hemolysis, which increases the risk of thrombosis. Appropriate device placement and anticoagulation management are imperative to help avoid neurological dysfunction and ischemic stroke, the most devastating potential complications of VAD therapy. As our experience grows, we continue to gain an increased understanding of the management of anticoagulation, need for antiplatelet medication, and appropriate monitoring for these critical patients.
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http://dx.doi.org/10.1055/s-0037-1607982DOI Listing
February 2018

Population Pharmacokinetics of Enoxaparin in Pediatric Patients.

Ann Pharmacother 2018 02 29;52(2):140-146. Epub 2017 Sep 29.

2 Baylor College of Medicine, Houston, TX, USA.

Background: There are no studies evaluating the pharmacokinetics of enoxaparin in the hospitalized pediatric patient population.

Objective: To characterize the pharmacokinetics of enoxaparin in pediatric patients.

Methods: A retrospective review of inpatients 1 to 18 years of age admitted to our institution who received enoxaparin with anti-factor Xa activity level monitoring was performed. Demographic variables, enoxaparin dosing, and anti-factor Xa activity levels were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. Simulation (n = 10 000) was performed to determine the percentage who achieved targeted anti-Xa levels at various doses.

Results: A total of 853 patients (male 52.1%, median age = 12.2 years; interquartile range [IQR] = 4.6-15.8 years) received a mean enoxaparin dose of 0.86 ± 0.31 mg/kg/dose. A median of 3 (IQR = 1-5) anti-factor Xa levels were sampled at 4.4 ± 1.3 hours after a dose, with a mean anti-factor Xa level of 0.52 ± 0.23 U/mL. A 1-compartment model best fit the data, and significant covariates included allometrically scaled weight, serum creatinine, and hematocrit on clearance, and platelets on volume of distribution. Simulations were run for patients both without and with reduced kidney function (creatinine clearance of ≤30 mL/min/1.73 m). A dose of 1 mg/kg/dose every 12 hours had the highest probability (72.3%) of achieving an anti-Xa level within the target range (0.5-1 U/mL), whereas a dose reduction of ~30% achieved the same result in patients with reduced kidney function.

Conclusions: Pediatric patients should initially be dosed at 1-mg/kg/dose subcutaneously every 12 hours for treatment of thromboembolism followed by anti-Xa activity monitoring. Dose reductions of ~30% for creatinine clearance ≤30 mL/min/1.73 m are required.
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http://dx.doi.org/10.1177/1060028017734234DOI Listing
February 2018

Enoxaparin Population Pharmacokinetics in the First Year of Life.

Ther Drug Monit 2017 12;39(6):632-639

*Department of Pharmacy, Texas Children's Hospital; †Department of Pediatrics, Baylor College of Medicine; ‡The Texas Medical Center Library; and §Department of Pathology and Transfusion Medicine, Baylor College of Medicine, Houston, Texas.

Aims: Enoxaparin dosing requirements in the first year of life can be highly variable. Characterization of pharmacokinetics in this patient population can assist in dosing.

Methods: Patients less than 1 year postnatal age who received enoxaparin and had an anti-factor Xa activity level drawn as inpatients were identified through the pharmacy database over a 5-year period. Patients on renal replacement therapy or with hyperbilirubinemia were excluded. Data collection included demographic variables, indication for enoxaparin, enoxaparin doses, anti-factor Xa activity levels, serum creatinine, hemoglobin, hematocrit, platelet count, and urine output over the previous 24 hours. Population pharmacokinetic analysis was performed with NONMEM.

Results: A total of 182 patients [male 50%, median 100 days postnatal age (range: 4-353 days)] met the study criteria. Patients received median 22 doses (range: 1-526) at a mean starting dose of 1.38 ± 0.43 mg/kg with median 5 (range: 1-56) anti-factor Xa activity levels measured. A 1-compartment proportional and additive error model best fits the data. Allometrically scaled weight significantly decreased the objective function value, as did serum creatinine on clearance, and postmenstrual age (PMA) on volume of distribution. When evaluated graphically, dosing based on PMA appeared to have less variability as compared to postnatal age-based dosing.

Conclusions: Dosing of enoxaparin in infants younger than 1 year should incorporate PMA.
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http://dx.doi.org/10.1097/FTD.0000000000000435DOI Listing
December 2017

Bleeding and Thrombotic Complications in the Use of Extracorporeal Membrane Oxygenation.

Semin Thromb Hemost 2018 Feb 12;44(1):20-29. Epub 2017 Sep 12.

Division of Transfusion Medicine & Coagulation, Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.

Extracorporeal membrane oxygenation (ECMO) has been used for >40 years to support lung and heart failure; however, bleeding and thrombosis remain serious complications. The known etiologies of bleeding include heparin effect or overdose, coagulopathy, thrombocytopenia, platelet dysfunction, acquired von Willebrand syndrome, and hyperfibrinolysis. Bleeding sites may include cannula insertion sites, recent surgical incisions, vascular access sites, lung, gastrointestinal tract, mouth, nose, thoracic cavity, abdominal cavity, and brain. Massive bleeding in the brain, the most feared bleeding complication, can be rapidly fatal because it occurs in a rigid closed space, is difficult to drain, and cannot be stopped with direct pressure to the bleeding site. Pulmonary hemorrhage may cause irreversible lung damage. Management should be swift and precise to prevent fatal bleeding. In contrast, etiologies of thrombosis include high fibrinogen and factor VIII levels, heparin resistance, and platelet activation. Achieving the optimal anticoagulation balance to prevent bleeding and thrombosis in ECMO patients is extremely complex. Experts in hemostasis should be a part of an institutional ECMO team and continuously available for immediate management.
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http://dx.doi.org/10.1055/s-0037-1606179DOI Listing
February 2018

Population pharmacokinetics of human antithrombin concentrate in paediatric patients.

Br J Clin Pharmacol 2017 Nov 11;83(11):2450-2457. Epub 2017 Aug 11.

Baylor College of Medicine, Department of Pediatrics, Houston, TX, USA.

Aims: Antithrombin is increasingly used in paediatric patients, yet there are few age-specific pharmacokinetic data to guide dosing. We aimed to describe the pharmacokinetic profile of human (plasma-derived) antithrombin concentrate in paediatric patients.

Methods: A 5-year retrospective review was performed of patients <19 years of age admitted to our institution who received antithrombin concentrate, were not on mechanical circulatory support and had baseline (predose) and postdose plasma antithrombin activity levels available for analysis. Demographic and laboratory variables, antithrombin dosing information and data on the use of continuous infusion unfractionated heparin were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. The model developed was tested against a validation dataset from a cohort of similar patients, and a predictive value was calculated.

Results: A total 184 patients met the study criteria {46.7% male, median age [years] 0.35 [interquartile range (IQR) 0.07-3.9]}. A median of two antithrombin doses (IQR 1-4) were given to patients (at a dose of 46.3 ± 13.6 units kg ), with median of three (IQR 2-7) postdose levels per patient. Continuous infusion unfractionated heparin was administered in 87.5% of patients, at a mean dose of 34.1 ± 22.7 units kg h . A one-compartment exponential error model best fit the data, and significant covariates included allometrically scaled weight on clearance and volume of distribution, unfractionated heparin dose on clearance, and baseline antithrombin activity level on volume of distribution. The model resulted in a median -1.75% prediction error (IQR -11.75% to 6.5%) when applied to the validation dataset (n = 30).

Conclusions: Antithrombin pharmacokinetics are significantly influenced by the concurrent use of unfractionated heparin and baseline antithrombin activity.
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http://dx.doi.org/10.1111/bcp.13359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651305PMC
November 2017

From Z to A: Putting Zika virus in perspective.

J Thorac Cardiovasc Surg 2017 07 9;154(1):303-304. Epub 2017 Feb 9.

Department of Pathology & Immunology, Baylor College of Medicine, Houston, Tex; Department of Pathology, Texas Children's Hospital, Houston, Tex. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2016.11.074DOI Listing
July 2017

Multidisciplinary team learning in the management of the morbidly adherent placenta: outcome improvements over time.

Am J Obstet Gynecol 2017 06 16;216(6):612.e1-612.e5. Epub 2017 Feb 16.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX.

Background: Morbidly adherent placenta (MAP) is a serious obstetric complication causing mortality and morbidity.

Objective: To evaluate whether outcomes of patients with MAP improve with increasing experience within a well-established multidisciplinary team at a single referral center.

Study Design: All singleton pregnancies with pathology-confirmed MAP (including placenta accreta, increta, or percreta) managed by a multidisciplinary team between January 2011 and August 2016 were included in this retrospective study. Turnover of team members was minimal, and cases were divided into 2 time periods so as to compare 2 similarly sized groups: T1 = January 2011 to April 2014 and T2 = May 2014 to August 2016. Outcome variables were estimated blood loss, units of red blood cell transfused, volume of crystalloid transfused, massive transfusion protocol activation, ureter and bowel injury, and neonatal birth weight. Comparisons and adjustments were made by use of the Student t test, Mann-Whitney U test, χ test, analysis of covariance, and multinomial logistic regression.

Results: A total of 118 singleton pregnancies, 59 in T1 and 59 in T2, were managed during the study period. Baseline patient characteristics were not statistically significant. Forty-eight of 59 (81.4%) patients in T1 and 42 of 59 (71.2%) patients in T2 were diagnosed with placenta increta/percreta. The median [interquartile range] estimated blood loss (T1: 2000 [1475-3000] vs T2: 1500 [1000-2700], P = .04), median red blood cell transfusion units (T1: 2.5 [0-7] vs T2: 1 [0-4], P = .02), and median crystalloid transfusion volume (T1: 4200 [3600-5000] vs T2: 3400 [3000-4000], P < .01) were significantly less in T2. Also, a massive transfusion protocol was instituted more frequently in T1: 15/59 (25.4%) vs 3/59 (5.1%); P < .01. Neonatal outcomes and surgical complications were similar between the 2 groups.

Conclusion: Our study shows that patient outcomes are improved over time with increasing experience within a well-established multidisciplinary team performing 2-3 cases per month. This suggests that small, collective changes in team dynamics lead to continuous improvement of clinical outcomes. These findings support the development of centers of excellence for MAP staffed by stable, core multidisciplinary teams, which should perform a significant number of these procedures on an ongoing basis.
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http://dx.doi.org/10.1016/j.ajog.2017.02.016DOI Listing
June 2017